Experimental Studies of Adhesion and Endocytosis of Calcium Oxalate Crystals in Renal Tubular Cells

Abstract

The present investigation was designed to study the interactions between Madin-Darby canine kidney (MDCK) cells and calcium oxalate monohydrate (COM) crystals, the most abundant constituent of urinary crystals, and to clarify the significance of these crystal-cell interactions in stone pathogenesis. COM crystals adhered to the intact surface of MDCK cells by some biological mechanisms (biological adhesion) and, were then internalized into the cell (endocytosis). The microvilli of the cell appeared to play an important role in this process. In the kidneys of rats with experimentally induced stones, most COM crystals adhered to the tubular cells and some crystals were engulfed, via endocytosis. Thus, these crystal-cell interactions might be one of the earliest processes in the formation of kidney stones. Further elucidation of the mechanism and the regulatory factors of this process may provide new insight into stone pathogenesis.

The effects of human urine on the adhesion of calcium oxalate crystal to Madin–Darby canine kidney cells

“…Lieske et al . [ 20] noted that microvilli appeared to play an important role in the adhesion and endocytosis of COM crystals, as also reported in our previous study [ 21]. Therefore, urine might have the potential to reduce crystal adhesion to cells by changing cell‐surface properties or microvilli function.…”

Crystals cause acute necrotic cell death in renal proximal tubule cells, but not in collecting tubule cells

“…In 1992, Lieske, Walsh-Reitz, and Toback [18] reported that the internalization of calcium oxalate monohydrate crystals by African green monkey (BSC-1) and MDCK cells stimulated DNA synthesis. Hackett, Shevock, and Khan [19] subsequently found that crystal-containing MDCK and LLC-PK 1 cells were rapidly released from the cultures, which was confirmed in other studies [4,18,[20][21][22][23][24][25]. Koul et al [1,26] found that calcium oxalate monohydrate activates p38 mitogen-activated protein kinase (MAPK) in LLC-PK 1 .…”

Alpha-enolase on apical surface of renal tubular epithelial cells serves as a calcium oxalate crystal receptor

“…Adhesion of COM crystals onto apical surface of renal tubular epithelial cells has been thought to be an early phase of stone nidus and kidney stone formation181920. Our previous expression proteomics study identified α-enolase as a COM crystal-binding protein on apical membranes of renal tubular epithelial cells by quadrupole time-of-flight (Q-TOF) tandem mass spectrometry (MS/MS)4.…”